Covalent modification of surface protein or carbohydrate

ABSTRACT

A chemo-physiological structure and method for forming the chemo-physiological structure. In a first embodiment, a cell of an animal is provided. The cell has a membrane surface and a viral receptor coupled to the membrane surface. A linker molecule having a covalently attached polymer is covalently bonded to the membrane surface, the viral receptor, or both. The polymer prevents an extracellular virus from bonding to the viral receptor. In a second embodiment, a linker molecule having a covalently attached polymer is covalently bonded to a capsid of a virus, which prevents the virus from bonding to a viral receptor of an adjacent or nearby animal cell.

BACKGROUND OF THE INVENTION

[0001] 1. Technical Field

[0002] The present invention relates generally to covalent modificationof surface protein or carbohydrate for protecting an animal againstviral attack.

[0003] 2. Related Art

[0004]FIG. 1 illustrates a cellular cross-sectional view of viraldisease pathogenesis, in accordance with the related art. FIG. 1 showscells 10 and 20 within an extracelluar environment 15. The cell 10comprises a cell interior 12, and a nucleus 11 within the cell interior12. A viral receptor 14 is coupled to a membrane surface 13 of the cell10. The cell 20 comprises a cell interior 22 and a nucleus 21 within thecell interior 22. A viral receptor 24 is coupled to a membrane surface23 of the cell 20.

[0005] An extracellular virus 1 in the extracellular environment 15enters the cell 10 through the viral receptor 14. While within the cellinterior 12 of the cell 10, the virus 1 undergoes multiple rounds ofreplication, resulting in the replication of viral DNA, RNA, and proteinfrom viruses 2, 3, 4, and 5, which: are packaged into their envelopes tobecome viruses 6, 7, 8, and 9, respectively; and pass through themembrane surface 13 into the extracellular environment 15.

[0006] The virus 9 enters the cell 20 through the viral receptor 24.While within the cell interior 22 of the cell 20, the virus 9 undergoesmultiple rounds of replication (not shown) in the cell interior 22 ofthe cell 20, and subsequently passes through the membrane surface 23enters the extracellular environment 15 as replicated viruses 27, 28,and 29.

[0007] Unfortunately, the viral replication in the cells 10 and 20, asdescribed supra, causes destruction of the cells 10 and 20 and possibleconsequent viral disease of an animal (i.e., a human or non-humananimal) that comprises the cells 10 and 20. Thus, there is a need toprevent such viral disease from occurring in the animal.

SUMMARY OF THE INVENTION

[0008] The present invention provides a chemo-physiological structure,comprising:

[0009] a membrane surface of a cell of an animal;

[0010] a viral receptor coupled to the membrane surface; and

[0011] a linker molecule covalently bonded to a tissue member selectedfrom the group consisting of the membrane surface, the viral receptor,and a combination thereof, wherein a polymer is covalently attached tothe linker molecule, and wherein the polymer prevents an extracellularvirus from bonding to the viral receptor.

[0012] The present invention provides a method for forming achemo-physiological structure, comprising:

[0013] providing a membrane surface of a cell of an animal and a viralreceptor coupled to the membrane surface; and

[0014] covalently bonding a linker molecule to a tissue member selectedfrom the group consisting of the membrane surface, the viral receptor,and a combination thereof, wherein a polymer is covalently attached tothe linker molecule, and wherein the polymer prevents an extracellularvirus from bonding to the viral receptor.

[0015] The present invention provides a chemo-physiological structure,comprising:

[0016] a virus having a capsid; and

[0017] a linker molecule covalently bonded to the capsid, wherein apolymer is covalently attached to the linker molecule, and wherein thepolymer envelops the virus in a manner that prevents the virus frombonding to a cell of an animal.

[0018] The present invention provides a method for forming achemo-physiological structure, comprising:

[0019] providing a virus having a capsid; and

[0020] covalently bonding a linker molecule to the capsid, wherein apolymer is covalently attached to the linker molecule, and wherein thepolymer envelops the virus in a manner that prevents the virus frombonding to a cell of an animal.

[0021] The present invention prevents a virus from recognizing the viralreceptors or the cell membrane of an animal cell, and thus from enteringan interior portion of the cell. Accordingly, the present inventionprotects the animal cell against viral attack and prevents viralinfection of the animal. The present invention may be used to preventviral infection in both human animals and non-human animals.

BRIEF DESCRIPTION OF THE DRAWINGS

[0022]FIG. 1 depicts a cellular cross-sectional view of viral diseasepathogenesis, in accordance with the related art.

[0023]FIG. 2 depicts a cellular cross-sectional view of how viraldisease may be prevented by using polymerated linker chemicals, inaccordance with the present invention.

[0024]FIG. 3 is enlarged view of a virus of FIG. 2 and its surroundingenvironment, in accordance with embodiments of the present invention.

[0025]FIG. 4 depicts an animal and modes of delivering a polymeratedlinker chemical therein, in accordance with embodiments of the presentinvention.

[0026]FIG. 5 lists exemplary viruses of human significance and ofveterinary significance, in accordance with embodiments of the presentinvention.

[0027]FIG. 6 depicts an exemplary chemistry of coupling the polymeratedlinker chemical of FIG. 2 or FIG. 3 to a protein, in accordance withembodiments of the present invention.

[0028]FIG. 7 lists exemplary polymeric linker compounds and associatedprotein or carbohydrate targets that can be covalently reacted with theexemplary polymeric linker compounds, for use in conjunction with FIG. 2and in accordance with embodiments of the present invention.

[0029]FIG. 8 is a bar graph showing the effect of covalent modificationof monkey kidney epithelial cells on the rate at which the cells becomeinfected with a virus.

[0030]FIG. 9 is a bar graph showing the effect of covalent modificationof Simian Vacuolating Agent (SV40) virus on the rate of viral infectionof monkey kidney epithelial cells located near the SV40 viruses.

[0031]FIG. 10 depicts a densitometry curve for a control sample for theSV40 virus of FIG. 9.

[0032]FIG. 11 depicts a densitometry curve for the covalently modifiedSV40 virus of FIG. 9.

DETAILED DESCRIPTION OF THE INVENTION

[0033]FIG. 2 illustrates a cellular cross-sectional view of how viraldisease may be prevented, in accordance with the present invention. FIG.2 shows cells 30 and 40 within an extracelluar environment 45. The cell30 comprises a cell interior 32, and a nucleus 31 within the cellinterior 32. A viral receptor 34 is coupled to a membrane surface 33 ofthe cell 30. The cell 40 comprises a cell interior 42, and a nucleus 41within the cell interior 42. A viral receptor 44 is coupled to amembrane surface 43 of the cell 40.

[0034] Also shown in FIG. 2 are extracellular viruses 55 and 56, whichare unable to access the viral receptors 34 and 44 because of a blockerlayer 54 and blocker envelopes 57 which are formed in accordance withthe present invention. By being so prevented from accessing the viralreceptors 34 and 44, the extracellular viruses 55 and 56 are said to be“inactivated.” The blocker layer 54 results from covalent bonding of apolymerated linker chemical 50 to the viral receptors 34 and themembrane surface 33 of the cell 30, and also to the viral receptors 44and the membrane surface 43 of the cell 40. The polymerated linkerchemical 50 includes a linker molecule 51 with a covalently attachedpolymer 52. The polymerated linker chemical 50 is said to represent anactivated form of the polymer 52 (e.g., if the polymer ismethylpolyethylene glycol (mPEG), then then “activated mPEG” isexemplified by having mPEG covalently bonded to the linker molecule ofcyanuric chloride). The linker molecule 51 is covalently bonded toproteins or carbohydrates in the viral receptors 34 and 44, and toproteins or carbohydrates in the membrane surfaces 33 and 43. Thecovalent linking of the linker molecule 51 to a protein may include acovalent linking of the linker molecule 51 to an amino acid in theprotein or to a sulfhydryl group in the protein. Thus, the linkermolecule 51, together with the covalently attached polymer 52, isdisposed between the virus 55 (or 56) and the viral receptors 34 and 44.The polymer 52 has a “long chain length;” i.e., a chain length that isof sufficient magnitude to fill the space around itself to create theblocker layer 54. Thus, the blocker layer 54 constitutes a barrier thatprevents the viruses 55 and 56 from having access to the viral receptors34 and 44. In addition, the polymer 52 within the blocker layer 54prevents the approach and binding of viruses by steric hindrance.Additionally, the polymer 52 may be highly hydrophillic so as to createa hydration zone around itself to alternatively create the blocker layer54. Inasmuch as the viruses 55 and 56 would covalently bond to the viralreceptors 34 and 44 via a charge-charge coupling mechanism, thehydration zone encompassed by the blocker layer 54 effectivelycamouflages molecular charge sites and thus prevents the viruses 55 and56 from having access to the viral receptors 34 and 44. Thus, thepolymer 52 effectively prevents the viruses 55 and 56 from recognizingthe viral receptors 34 and 44 and thus from entering an interior portionof the cell 30 and of the cell 40.

[0035] The blocker envelope 57 results from covalent bonding of apolymerated linker chemical 59 with the virus 56. The polymerated linkerchemical 59 includes a linker molecule 61 with a covalently attachedpolymer 62. The polymerated linker chemical 59 may be the same as (i.e.,chemically identical to), or different from, the polymerated linkerchemical 50. The linker molecule 61 is covalently bonded to proteins orcarbohydrates in an outer portion (i.e., the capsid) of the virus 56.The polymer 62 has a “long chain length;” i.e., a chain length that isof sufficient magnitude to fill the space around itself to create theblocker envelope 57. Thus, the blocker envelope 57 constitutes a barrierthat prevents the virus 56 from having access to the viral receptors 34and 44 even if the blocker layer 54 were absent. In addition, thepolymer 52 within the blocker layer 54 prevents, by steric hindrance,the virus 56 from approaching, and binding to, animal cells.Additionally, the polymer 62 may be highly hydrophillic so as to createa hydration zone around itself to alternatively create the blockerenvelope 57. Inasmuch as the virus 56 would covalently bond to the viralreceptors 34 and 44 via a charge-charge coupling mechanism, thehydration zone encompassed by the blocker envelope 57 effectivelycamouflages molecular charge sites and thus prevents the virus 56 fromhaving access to the viral receptors 34 and 44 even if the blocker layer54 were absent. Thus, the polymer 62 effectively prevents the virus 56from recognizing the viral receptors 34 and 44 and thus from entering aninterior portion of the cell 30 and of the cell 40.

[0036]FIG. 3 is enlarged view of the virus 56 and blocker envelope 57 ofFIG. 2, in accordance with embodiments of the present invention. Thevirus 56 includes a viral core 47 and a capsid 48. The viral core 47includes genetic material (i.e., DNA or RNA). The capsid 48 is a shellcomprising protein. Some viruses additionally include an outer lipidenvelope (not shown) that surrounds the capsid. FIG. 3 shows that thelinker molecule 61 of the polymerated linker chemical 59 is covalentlybonded to the capsid 48. In particular, the polymerated linker chemical59 may be covalently bonded to an amino acid (e.g., lysine), asulfhydryl group, or a carbohydrate at the capsid 48. The polymer 62 ofthe polymerated linker chemical 59 envelops the virus 56 in a mannerthat prevents the virus 56 from bonding to a cell (and from entering thecell) of an animal.

[0037] The cells 30 and 40 of FIG. 2 may be treated in vivo within ananimal 60 (see FIG. 4) with the polymerated linker chemical 50 or 59 (orboth) for clinical purposes such for preventing or treating a viralinfection. FIG. 4 shows the animal 60 having an epithelium 17 (i.e.,membranous cellular tissue at external surfaces of the animal 60 or“skin”), an interior 18, openings 63 and 64, an organ 65 coupled to theopening 63, a muscle 66, and a blood vessel 67. The animal 60 may be ahuman animal (e.g., a human being or a fetus) or a veterinary animal. Aveterinary animal is a non-human animal of any kind such as, inter alia,a domestic animal (e.g., dog, cat, etc.), a farm animal (cow, sheep,pig, etc.), a wild animal (e.g., a deer, fox, etc.), a laboratory animal(e.g., mouse, rat, monkey, etc.), an aquatic animal (e.g., a fish,turtle, etc.), etc. The openings 63 and 64 include a cell 73 and 74,respectively, the organ 65 includes a cell 75, the muscle 66 includes acell 76, and the blood vessel 67 includes a cell 77. The blood vessel 67is part of a systemic vascular system (not shown) capable oftransporting polymerated linker chemical 50 or 59 (or both) to cellsdistributed throughout the animal 60. The openings 63 and 64 include anyopening that pertains to the animal 60. If the animal 60 is a humanbeing, for example, then the openings 63 and 64 may include, inter alia,a nasal cavity, a mouth, a vagina if the animal 60 is female, etc. Theorgan 65 includes any organ that pertains to the animal 60. If theanimal 60 is a human being, for example, then the organ 65 may include,inter alia, a lung, a stomach, a kidney, a liver, etc. The organ 65 maybe coupled to the opening 63 or 64, or may rather be coupled to theblood vessel 67 through the systemic vascular system of the animal 60.FIG. 4 also shows viruses 35, 36, 37, 38, and 39 in the opening 63, theopening 64, the muscle 66, the blood vessel 67, and the organ 65,respectively.

[0038] A polymerated linker chemical (PLC) 68 may be delivered to anycell of the animal 60 where viral infection is possible such as, interalia, to any of the cells 73-77, or to extracellular viruses in anyopening (e.g., the openings 63 and 64), in any organ (e.g., the organ65), in any muscle (e.g., the muscle 66), in any blood vessel (e.g., theblood vessel 67), or in any other relevant location such as a peritonealcavity, etc. Said delivery of the PLC 68 may be accomplished in anymanner known to one of ordinary skill in the art such as, inter alia,via spray bottle 70 into the opening 63, via syringe 71 into the opening64, via needle 72 into the muscle 66, and via intravenous deliveryapparatus 69 into the blood vessel 67. A spray of the PLC 68 from thespray bottle 70 may be, inter alia, aerosol activated.

[0039] There are numerous examples of how the PLC 68 may be delivered tocells of the animal 60 or to viruses within the animal 60. As a firstexample, the PLC 68 may be packaged within the spray bottle 70 andsprayed into a nasal cavity as represented by the opening 63, where thePLC 68 generates a blocker layer (see, e.g., the blocker layer 54 ofFIG. 2) on the nasal epithelial cell 73 in the nasal cavity 63, and ablocker envelope (see, e.g., the blocker envelope 57 of FIG. 2) over anyextracellular virus that is present in the nasal cavity 63. The PLC 68from the spray bottle 70, after being sprayed into the nasal cavityrepresented by the opening 63, may be inhaled into a lung as representedby the organ 65, where the PLC 68 generates a blocker layer on thepulmonary cell 75 in the lung, and a blocker envelope over anyextracellular virus that is present in the lung. As a second example,the PLC 68 in the spray bottle 70 may be sprayed into a mouth asrepresented by the opening 63, and may be inhaled into a lung asrepresented by the organ 65, where the PLC 68 generates a blocker layeron the cell 75 in the lung, and a blocker envelope over anyextracellular virus that is present in the lung. As a third example, thePLC 68 in the syringe 71 may be delivered to a vagina as by the opening64, where the PLC 68 generates a blocker layer on the vaginal cell 74 inthe vagina, and a blocker envelope over any extracellular virus that ispresent in the vagina. Any mechanism discussed supra in conjunction withFIG. 2 for inactivating any of the viruses in FIG. 2 may be utilized forinactivating any of the viruses in FIG. 4.

[0040] The cells 30 and 40 of FIG. 2 may be alternatively removed fromthe animal 60 of FIG. 4 and treated in vitro (i.e., outside of theanimal) with the PLC 50 or 59, or both (see FIG. 2), such as in alaboratory setting for such purposes as, inter alia, research ortesting. The PLC 50 or 59, or both may be delivered in vitro to any cellof the animal 60 that has been so removed from any portion of the animal60, such as to, inter alia, any of the cells 73-77 of FIG. 4, in anymanner known to one of ordinary skill in the art such as, inter alia, byspraying the PLC 50 or 59, or both on the cells, or by immersion of thecells into a liquid that includes the PLC 50 or 59, or both, to form ablocker layer on the cells. In addition, the PLC 50 or 59, or both, maybe delivered in vitro to viruses in the vicinity of the cells so removedfrom the animal 60 of FIG. 4, in any manner known to one of ordinaryskill in the art such as, inter alia, by spraying the PLC 50 or 59, orboth, on or near the viruses to form blocker envelopes around theviruses.

[0041]FIGS. 2, 3, and 4 show “chemo-physiological structures.” Achemo-physiological structure is defined herein as an organic structurethat includes at least one organism (e.g., an animal, a cell, a virus,or any portion thereof) and any chemical that is covalently bonded toany organism of the at least one organism.

[0042] As discussed supra in conjunction with FIGS. 2 and 3, the presentinvention uses a polymerated linker chemical 50 or 59 to generate theblocker layer 54 and the blocker envelope 57, respectively, toinactivate the extracellular viruses 55 and 56 by preventing theextracellular viruses 55 and 56 from bonding with viral receptors 33 and44 which are coupled to cells 30 and 40, respectively. The use of theblocker layer 54 and the blocker envelope 57 is non-specific as to thetype of virus that is inactivated and any virus that can infect ananimal (human or non-human) can be inactivated in accordance with thepresent invention. FIG. 5 tabulates examples of viruses that can beinactivated in accordance with the present invention. Each listed virusin FIG. 5 is classified as to whether said listed virus is of humansignificance or of veterinary significance. A virus is of humansignificance if the virus is known to one of ordinary skill in the artas being capable of infecting a human animal. A virus is of veterinarysignificance if the virus known to one of ordinary skill in the art asbeing capable of infecting a non-human animal. The list of viruses inFIG. 5 is merely exemplary. Numerous viruses other than those listed inFIG. 5 can be inactivated in accordance with the present invention.

[0043]FIG. 6 illustrates an exemplary chemistry of coupling thepolymerated linker chemical, as depicted in FIG. 2 or FIG. 3, to aprotein, in accordance with embodiments of the present invention. InFIG. 6, two chemical reactions are illustrated. In the first chemicalreaction shown in FIG. 6, a polymer 80 reacts with a linker molecule 81to form a polymeric linker chemical (PLC) 82 in which the polymer 80 iscovalently bonded to the linker molecule 81. Specifically in FIG. 6, thepolymer 80 is methoxypolyethylene glycol (mPEG) having the chemicalstructure of CH₃(—O—CH₂—CH₂)_(n)—OH wherein n≧2. The linker molecule 81is an alkyl halide (namely, cyanuric acid) and the resultant PLC 82 is2-O-mPEG-4,6-dichloro-s-triazine. In the first chemical reaction, thehydroxyl group (OH⁻) is a nucleophile that reacts generally with analkyl halide (specifically, cyanuric chloride), resulting indisplacement and release of the chlorine ion (CL⁻) in position 2 of thecyanuric chloride triazine ring as well as release of the hydrogen ion(H⁻) from the hydroxy group of the mPEG. The first chemical reaction maybe implemented in any manner known to one of ordinary skill in the artsuch as in, inter alia, anhydrous benzene at a temperature of about 25°C. Formation of the PLC 82 of 2-O-mPEG-4,6-dichloro-s-triazine iswell-known in the art and may be obtained commercially.

[0044] In the second chemical reaction shown in FIG. 6, a protein 83reacts with the PLC 82 to form a protein-polymer complex 84.Specifically in FIG. 6, the protein 83 includes lysine, whereinH₃N⁺—(CH₂)₄ is a portion of the lysine that reacts with the PLC 82, andwherein X represents a remaining portion of the protein 83 including aremaining portion of the lysine. The remaining portion of the lysine hasa carbon atom covalently bonded to H, H₃N⁺, and a carboxyl group. Asshown in FIG. 6, a hydrolysis of the chlorine in position 4 of thecyanuric chloride triazine ring has replaced said chlorine in position 4with the H₃N⁺—(CH₂)₄ portion of the lysine of the protein 83, to formthe protein-polymer complex 84. Specifically in FIG. 6, theprotein-polymer complex 84 is 2-O-mPEG-4-Y-6-chloro-s-triazine, whereinY is the protein H₃N⁺—(CH₂)₄—X. More generally, FIG. 6 shows generationof a PEG-conjugated protein with attachment of an activated PEG (e.g.,the PLC 82) to an ε-amino group (e.g., the lysine or another amino acidsuch as arginine). The second chemical reaction may be implemented in analkaline phosphate buffer (e.g., 50 mM of K₂HPO₄ and 105 mM of NaCl,wherein mM denotes millimoles). The second reaction can be efficientlyaccomplished in a wide range of media including, inter alia, saline,phosphate buffered saline, blood plasma, blood serum, albumin containingbuffers, Hanks Balanced Salt Solution (HBSS),N-[2-hydroxyethyl]piperazine-N′-2-ethanesulfonic acid (“HEPES”), RoswellPark Memorial Institute 1640 (“RPMI 1640”), etc.

[0045] Time and temperature for performing the second reaction are veryflexible. For example, a reaction between mPEG and amino acid of cellmembranes or cell viral receptors may be accomplished in 4 minutes orlonger at 4° C. if the pH is about 9. If the pH is lower (e.g., about8), the reaction may proceed at room temperature for a longer period(e.g., 60 minutes or longer) so that the cells are not stressed bytemperature and not stressed by harsh alkaline conditions. As to pH, itis useful to have a pH of about 8 when reacting mPEG with lysine. Whenreacting mPEG with a virus, weakly acidic to alkaline conditions shouldbe used with a representative pH range of about 6.0 to about 9.0. Whenreacting mPEG with a living cell, a suitable pH range is cell specificfor the particular type of living cell being reacted.

[0046] Effective doses of the PLC in the second reaction depend onseveral variables, including: linker chemistry, the polymer being used,surface area of cell membranes being modified, density of viralreceptors, geometric factors such as available volume above the cellsbeing modified (e.g., a higher dose may be needed to cover an uppernasal cavity than a low nasal cavity), etc.

[0047] It should be noted that the chlorine in position 6 of thecyanuric chloride triazine ring is quite unreactive and thus unavailableto react with either an amino acid or with a second polymerated linkerchemical.

[0048]FIG. 6 illustrates a mechanism of the covalent attachment of thePLC of cyanuric chloride coupled mPEG with membrane proteins, andpotentially membrane carbohydrates. Virtually all cells and proteins canbe similarly modified (e.g., red blood cells, platelets, endothelialcells, epithelial cells, stromal cells) with only slight variations inpH, temperature and time. Indeed, the pH, time and temperatureconditions at which the modification reaction can be done at are verymalleable, thus making this invention applicable to a wide variety ofcell types. Other polymers may be utilized instead of mPEG, such as,inter alia, polyethylene glycol, ethoxypolyethylene glycol, dextran,ficoll, and arabinogalactan. Other linker molecules may be utilizedinstead of cyanuric chloride, such as, inter alia, imidazolyl formate,succinimidyl succinate, succinimidyl glutarate, N-hydroxysuccinimide,4-Nitrophenol, 2,4,5-trichlorophenol, and a chloroformate. FIG. 7 listsexemplary polymeric linker compounds (PLCs) that may be used with thepresent invention and associated targets that can be reacted with thePLCs. Most of the listed targets in FIG. 7 are proteins. The thiolgroups in FIG. 7 include sulfhydryl groups which are protein components.Any of the PLCs that react with the hydroxyl group can be reacted with acarbohydrate. Note that the PLC of phospholipid PEG interacts with alipid by intercalation rather than by covalent bonding.

[0049] The present invention is illustrated by the followingnon-limiting examples.

EXAMPLE 1

[0050] Epithelial monolayers of monkey kidney CV1 cells were covalentlymodified with activated mPEG (i.e., mPEG covalently bonded to a cyanuricchloride linker molecule). In particular, the cells were confluentlygrown on glass slides. The cells were then exposed to a solution ofactivated mPEG, followed by exposure to Simian Vacuolating Agent (SV40)virus for 72 hours in a medium of Minimum Essential Medium (MEM). Itshould be noted that the SV40 virus has veterinary significance, butdoes not have human significance.

[0051]FIG. 8 is a bar graph that shows the percentage of CV1 cellsinfected after 24 hours, as assayed via T antigen staining.Concentrations of 12 and 25 milligrams (mg) of mPEG per milliliter (ml)of medium were each analyzed. Control cells, which are notmPEG-modified, were infected at a rate of nearly 50% at 24 hours ofexposure to the SV40 virus. In contrast, the 12 and 25 mg/ml samples ofmPEG-modified cells were infected at a rate of only 5% and 1%,respectively, at 24 hours of exposure to the SV40 virus.

[0052] The results of this test support covalently bonding a polymeratedlinker chemical (e.g., activated mPEG) to membrane cell surfaces toprevent viral infection of the cells. While this test utilized mPEG as apolymer in the polymerated linker chemical, any other polymer discussedherein could have been used instead of mPEG. Similarly, while this testutilized cyanuric chloride as a linker molecule in the polymeratedlinker chemical, any other linker molecule discussed herein could havebeen used instead of cyanuric chloride. Although this test utilizedmonkey kidney CV1 cells, cells of other animal species (or cells of amonkey other than monkey kidney cells), could have been used instead ofthe monkey kidney CV1 cells.

EXAMPLE 2

[0053] SV40 virus was covalently modified with a polymerated linkerchemical of activated mPEG (i.e., mPEG covalently bonded to a cyanuricchloride linker molecule) in Minimal Essential Medium (MEM) (a Cellgro®cell media product by Mediatech, Inc.), supplemented with 5% fetalbovine serum (FBS) and MEM vitamins and mineral supplement. The SV40viruses were modified at room temperature for a period of either 30minutes or 60 minutes. Next, epithelial monolayers of monkey kidney CV1cells were exposed to the covalently modified SV40 virus for 72 hours ina medium of MEM.

[0054]FIG. 9 is a bar graph that shows the percentage of CV1 cellsinfected after 24 hours, 48 hours, and 72 hours of SV40 virus exposure,as assayed via T antigen staining. The “I” above and below each bardenotes a standard deviation. Concentration of 0.1, 0.5, 1.0, 2.0, 3.0,5.0, 10.0, and 20.0 mg/ml of mPEG, at a pH of 8.0, were each analyzed.C1 and C2 represent control cells not mPEG-modified, having a pH of 7.4and 8.0 respectively. The control cells had a rate 35%-40% infectionrate at 24 hours and nearly a 100% infection rate at 72 hours. The mPEGmodified cells had an infection rate that decreased with concentrationof mPEG. At the highest mPEG concentration of 20 milligrams/milliliter,the infection rate was only about 10% at 72 hours of SV40 virusexposure.

[0055]FIGS. 10 and 11 depict densitometry curves, based on sodiumdodecyl sulfate (SDS) polyacrylamide gel electrophoresis, that show anextent to which the SV40 virus has been covalently mPEG modified in thetests of FIG. 9. FIG. 10 depicts a densitometry curve for a controlsample (C1 or C2 of FIG. 9) for the SV40 virus of FIG. 9. As statedsupra, the control samples have not been mPEG modified. The “A” portionof the densitometry curve of FIG. 10 represents a VP1 protein of theSV40 viral capsid, as detected by an anti-VP1 antibody. The indicatedvalue of 3816 represents the area under the curve of the “A” portionthat denotes the VP1 antibody response and serves as a reference valuefor subsequent comparison purposes.

[0056]FIG. 11 depicts a densitometry curve for the covalentlymPEG-modified SV40 virus of FIG. 9. The “A” portion of the densitometrycurve of FIG. 11 represents a VP1 protein of the SV40 viral capsid andthe indicated area of 3235 represents a small decrease in VP1 antibodyresponse”. The “B1”, “B2”, and “B3” portions of the densitometry curveof FIG. 11 respectively represents an antibody response to 1 mPEG, 2mPEGs, and 3 mPEGs, covalently bonded to a single protein. The indicatedvalues of 2557, 406, and 724 for the areas under the B1, B2, and B3curves, respectively, denote relative abundances of the 1 mPEG-modifiedproteins, 2 mPEG-modified proteins, and 3 mPEG-modified proteins. Thepresence of the B1, B2, and B3 portions of the densitometry curve ofFIG. 11, and the absence of B1, B2, and B3 portions in the controlsample of FIG. 10, demonstrates that covalent bonding of the SV40 viruswith activated mPEG indeed occurred for the tests of FIG. 9.

[0057] The results of this test support covalently bonding a polymeratedlinker chemical (e.g., activated mPEG) to a virus so as to inactivate anability of the virus to infect adjacent or nearby cells of an animal.While this test utilized mPEG as a polymer in the polymerated linkerchemical, any other polymer discussed herein could have been usedinstead of mPEG. Similarly, while this test utilized cyanuric chlorideas a linker molecule in the polymerated linker chemical, any otherlinker molecule discussed herein could have been used instead ofcyanuric chloride. Although this test utilized monkey kidney CV1 cells,cells of other animal species (or cells of a monkey other than monkeykidney cells), could have been used instead of the monkey kidney CV1cells.

[0058] While particular embodiments of the present invention have beendescribed herein for purposes of illustration, many modifications andchanges will become apparent to those skilled in the art. Accordingly,the appended claims are intended to encompass all such modifications andchanges as fall within the true spirit and scope of this invention.

What is claimed is:
 1. A chemo-physiological structure, comprising: amembrane surface of a cell of an animal; a viral receptor coupled to themembrane surface; and a linker molecule covalently bonded to a tissuemember selected from the group consisting of the membrane surface, theviral receptor, and a combination thereof, wherein a polymer iscovalently attached to the linker molecule, and wherein the polymerprevents an extracellular virus from bonding to the viral receptor. 2.The chemo-physiological structure of claim 1, further comprising theextracellular virus, wherein the linker molecule together with thecovalently attached polymer is disposed between the virus and the viralreceptor.
 3. The chemo-physiological structure of claim 1, wherein thepolymer is selected from the group consisting of polyethylene glycol,methoxypolyethylene glycol, ethoxypolyethylene glycol, dextran, ficoll,and arabinogalactan.
 4. The chemo-physiological structure of claim 1,wherein the linker molecule is selected from the group consisting ofcyanuric chloride, imidazolyl formate, succinimidyl succinate,succinimidyl glutarate, N-hydroxysuccinimide, 4-Nitrophenol,2,4,5-trichlorophenol, and a chloroformate.
 5. The chemo-physiologicalstructure of claim 1, further comprising the extracellular virus,wherein the virus has human significance.
 6. The chemo-physiologicalstructure of claim 1, further comprising the extracellular virus,wherein the virus has veterinary significance.
 7. Thechemo-physiological structure of claim 1, wherein the linker molecule iscovalently bonded to an amino acid at the tissue member.
 8. Thechemo-physiological structure of claim 1, wherein the linker molecule iscovalently bonded to a lysine group at the tissue member.
 9. Thechemo-physiological structure of claim 1, wherein the linker molecule iscovalently bonded to a carbohydrate at the tissue member.
 10. Thechemo-physiological structure of claim 1, wherein the linker molecule iscovalently bonded to a sulfhydryl group at the tissue member.
 11. Achemo-physiological structure, comprising: a membrane surface of a cellof an animal; a viral receptor coupled to the membrane surface; and alinker molecule covalently bonded to the membrane surface, wherein apolymer is covalently attached to the linker molecule, and wherein thepolymer prevents an extracellular virus from bonding to the viralreceptor.
 12. A chemo-physiological structure, comprising: a membranesurface of a cell of an animal; a viral receptor coupled to the membranesurface; and a linker molecule covalently bonded to the viral receptor,wherein a polymer is covalently attached to the linker molecule, andwherein the polymer prevents an extracellular virus from bonding to theviral receptor.
 13. A chemo-physiological structure, comprising: amembrane surface of a cell of an animal, said cell selected from thegroup consisting of an epithelial cell and an endothelial cell; a viralreceptor coupled to the membrane surface; and a linker moleculecovalently bonded to a tissue member selected from the group consistingof the membrane surface, the viral receptor, and a combination thereof,wherein a polymer is covalently attached to the linker molecule, andwherein the polymer prevents an extracellular virus from bonding to theviral receptor.
 14. A chemo-physiological structure, comprising: amembrane surface of a nasal epithelial cell of an animal; a viralreceptor coupled to the membrane surface; and a linker moleculecovalently bonded to a tissue member selected from the group consistingof the membrane surface, the viral receptor, and a combination thereof,wherein a polymer is covalently attached to the linker molecule, andwherein the polymer prevents an extracellular virus from bonding to theviral receptor.
 15. A chemo-physiological structure, comprising: amembrane surface of a pulmonary cell of an animal; a viral receptorcoupled to the membrane surface; and a linker molecule covalently bondedto a tissue member selected from the group consisting of the membranesurface, the viral receptor, and a combination thereof, wherein apolymer is covalently attached to the linker molecule, and wherein thepolymer prevents an extracellular virus from bonding to the viralreceptor.
 16. A chemo-physiological structure, comprising: a membranesurface of a vaginal cell of an animal; a viral receptor coupled to themembrane surface; and a linker molecule covalently bonded to a tissuemember selected from the group consisting of the membrane surface, theviral receptor, and a combination thereof, wherein a polymer iscovalently attached to the linker molecule, and wherein the polymerprevents an extracellular virus from bonding to the viral receptor. 17.A chemo-physiological structure, comprising: an animal; a membranesurface of a cell within the animal; a viral receptor coupled to themembrane surface; and a linker molecule covalently bonded to a tissuemember selected from the group consisting of the membrane surface, theviral receptor, and a combination thereof, wherein a polymer iscovalently attached to the linker molecule, and wherein the polymerprevents an extracellular virus from bonding to the viral receptor. 18.A chemo-physiological structure, comprising: a human animal; a membranesurface of a cell within the human animal; a viral receptor coupled tothe membrane surface; and a linker molecule covalently bonded to atissue member selected from the group consisting of the membranesurface, the viral receptor, and a combination thereof, wherein apolymer is covalently attached to the linker molecule, and wherein thepolymer prevents an extracellular virus from bonding to the viralreceptor.
 19. A chemo-physiological structure, comprising: a veterinaryanimal; a membrane surface of a cell within the veterinary animal; aviral receptor coupled to the membrane surface; and a linker moleculecovalently bonded to a tissue member selected from the group consistingof the membrane surface, the viral receptor, and a combination thereof,wherein a polymer is covalently attached to the linker molecule, andwherein the polymer prevents an extracellular virus from bonding to theviral receptor.
 20. A chemo-physiological structure, comprising: amembrane surface of a cell of an animal; a viral receptor coupled to themembrane surface; and a linker molecule covalently bonded to a tissuemember selected from the group consisting of the membrane surface, theviral receptor, and a combination thereof, wherein a polymer iscovalently attached to the linker molecule, and wherein the polymer hasa long chain length that prevents an extracellular virus from bonding tothe viral receptor.
 21. A chemo-physiological structure, comprising: amembrane surface of a cell of an animal; a viral receptor coupled to themembrane surface; and a linker molecule covalently bonded to a tissuemember selected from the group consisting of the membrane surface, theviral receptor, and a combination thereof, wherein a polymer iscovalently attached to the linker molecule, and wherein the polymerinactivates a charge-charge interaction that would otherwise bind anextracellular virus to the viral receptor.
 22. A chemo-physiologicalstructure, comprising: a membrane surface of a cell of an animal; aviral receptor coupled to the membrane surface; and a linker moleculecovalently bonded to a tissue member selected from the group consistingof the membrane surface, the viral receptor, and a combination thereof,wherein a polymer is covalently attached to the linker molecule, andwherein the polymer prevents an extracellular virus from entering aninterior portion of the cell.
 23. A method for forming achemo-physiological structure, comprising: providing a membrane surfaceof a cell of an animal and a viral receptor coupled to the membranesurface; and covalently bonding a linker molecule to a tissue memberselected from the group consisting of the membrane surface, the viralreceptor, and a combination thereof, wherein a polymer is covalentlyattached to the linker molecule, and wherein the polymer prevents anextracellular virus from bonding to the viral receptor.
 24. The methodof claim 23, further comprising providing the extracellular virus,wherein the linker molecule together with the covalently attachedpolymer is disposed between the virus and the viral receptor.
 25. Themethod of claim 23, wherein the polymer is selected from the groupconsisting of polyethylene glycol, methoxypolyethylene glycol,ethoxypolyethylene glycol, dextran, ficoll, and arabinogalactan.
 26. Themethod of claim 23, wherein the linker molecule is selected from thegroup consisting of cyanuric chloride, imidazolyl formate, succinimidylsuccinate, succinimidyl glutarate, N-hydroxysuccinimide, 4-Nitrophenol,2,4,5-trichlorophenol, and a chloroformate.
 27. The method of claim 23,further comprising providing the extracellular virus, wherein the virushas human significance.
 28. The method of claim 23, further comprisingproviding the extracellular virus, wherein the virus has veterinarysignificance.
 29. The method of claim 23, wherein covalently bonding thelinker molecule to the tissue member includes covalently bonding thelinker molecule to an amino acid at the tissue member.
 30. The method ofclaim 23, wherein covalently bonding the linker molecule to the tissuemember includes covalently bonding the linker molecule to a lysine groupat the tissue member.
 31. The method of claim 23, wherein covalentlybonding the linker molecule to the tissue member includes covalentlybonding the linker molecule to a carbohydrate at the tissue member. 32.The method of claim 23, wherein covalently bonding the linker moleculeto the tissue member includes covalently bonding the linker molecule toa sulfhydryl group at the tissue member.
 33. A method for forming achemo-physiological structure, comprising: providing a membrane surfaceof a cell of an animal and a viral receptor coupled to the membranesurface; and covalently bonding a linker molecule bonded to the membranesurface, wherein a polymer is covalently attached to the linkermolecule, and wherein the polymer prevents an extracellular virus frombonding to the viral receptor.
 34. A method for forming achemo-physiological structure, comprising: providing a membrane surfaceof a cell of an animal and a viral receptor coupled to the membranesurface; and covalently bonding a linker molecule bonded to the viralreceptor, wherein a polymer is covalently attached to the linkermolecule, and wherein the polymer prevents an extracellular virus frombonding to the viral receptor.
 35. A method for forming achemo-physiological structure, comprising: providing a membrane surfaceof a cell of an animal and a viral receptor coupled to the membranesurface, said cell selected from the group consisting of an epithelialcell and an endothelial cell; and covalently bonding a linker moleculeto a tissue member selected from the group consisting of the membranesurface, the viral receptor, and a combination thereof, wherein apolymer is covalently attached to the linker molecule, and wherein thepolymer prevents an extracellular virus from bonding to the viralreceptor.
 36. A method for forming a chemo-physiological structure,comprising: providing a membrane surface of a nasal epithelial cell ofan animal and a viral receptor coupled to the membrane surface; andcovalently bonding a linker molecule to a tissue member selected fromthe group consisting of the membrane surface, the viral receptor, and acombination thereof, wherein a polymer is covalently attached to thelinker molecule, and wherein the polymer prevents an extracellular virusfrom bonding to the viral receptor.
 37. A method for forming achemo-physiological structure, comprising: providing a membrane surfaceof a pulmonary cell of an animal and a viral receptor coupled to themembrane surface; and covalently bonding a linker molecule to a tissuemember selected from the group consisting of the membrane surface, theviral receptor, and a combination thereof, wherein a polymer iscovalently attached to the linker molecule, and wherein the polymerprevents an extracellular virus from bonding to the viral receptor. 38.A method for forming a chemo-physiological structure, comprising:providing a membrane surface of a vaginal cell of an animal and a viralreceptor coupled to the membrane surface; and covalently bonding alinker molecule to a tissue member selected from the group consisting ofthe membrane surface, the viral receptor, and a combination thereof,wherein a polymer is covalently attached to the linker molecule, andwherein the polymer prevents an extracellular virus from bonding to theviral receptor.
 39. A method for forming a chemo-physiologicalstructure, comprising: providing an animal having a cell such that aviral receptor is coupled to a membrane surface of the cell; andcovalently bonding a linker molecule to a tissue member selected fromthe group consisting of the membrane surface, the viral receptor, and acombination thereof, wherein a polymer is covalently attached to thelinker molecule, and wherein the polymer prevents an extracellular virusfrom bonding to the viral receptor.
 40. A method for forming achemo-physiological structure, comprising: providing a human animalhaving a cell such that a viral receptor is coupled to a membranesurface of the cell; and covalently bonding a linker molecule to atissue member selected from the group consisting of the membranesurface, the viral receptor, and a combination thereof, wherein apolymer is covalently attached to the linker molecule, and wherein thepolymer prevents an extracellular virus from bonding to the viralreceptor.
 41. A method for forming a chemo-physiological structure,comprising: providing a veterinary animal having a cell such that aviral receptor is coupled to a membrane surface of the cell; andcovalently bonding a linker molecule to a tissue member selected fromthe group consisting of the membrane surface, the viral receptor, and acombination thereof, wherein a polymer is covalently attached to thelinker molecule, and wherein the polymer prevents an extracellular virusfrom bonding to the viral receptor.
 42. A method for forming achemo-physiological structure, comprising: providing a membrane surfaceof a cell of an animal and a viral receptor coupled to the membranesurface; and covalently bonding a linker molecule to a tissue memberselected from the group consisting of the membrane surface, the viralreceptor, and a combination thereof, wherein a polymer is covalentlyattached to the linker molecule, and wherein the polymer has a longchain length that prevents an extracellular virus from bonding to theviral receptor.
 43. A method for forming a chemo-physiologicalstructure, comprising: providing a membrane surface of a cell of ananimal and a viral receptor coupled to the membrane surface; andcovalently bonding a linker molecule to a tissue member selected fromthe group consisting of the membrane surface, the viral receptor, and acombination thereof, wherein a polymer inactivates a charge-chargeinteraction that would otherwise bind an extracellular virus to theviral receptor.
 44. A method for forming a chemo-physiologicalstructure, comprising: providing a membrane surface of a cell of ananimal and a viral receptor coupled to the membrane surface; andcovalently bonding a linker molecule to a tissue member selected fromthe group consisting of the membrane surface, the viral receptor, and acombination thereof, wherein a polymer is covalently attached to thelinker molecule, and wherein the polymer prevents an extracellular virusfrom entering an interior portion of the cell.
 45. A method for forminga chemo-physiological structure, comprising: providing an animal havinga cell on a membrane surface, said cell having a viral receptor, saidcell selected from the group consisting of an epithelial cell and anendothelial cell; and introducing a linker molecule into the animal,said linker molecule having a polymer covalently attached thereto,wherein said introducing results in the linker molecule being covalentlybonded to the membrane surface such that the polymer prevents anextracellular virus from bonding to the viral receptor.
 46. A method forforming a chemo-physiological structure, comprising: providing an animalhaving a nasal cavity, said nasal cavity having a nasal epithelial cellon an nasal membrane surface, said cell having a viral receptor; andspraying a linker molecule into the nasal cavity, said linker moleculehaving a polymer covalently attached thereto, wherein the sprayingresults in the linker molecule being covalently bonded to the membranesurface such that the polymer prevents an extracellular virus frombonding to the viral receptor.
 47. A method for forming achemo-physiological structure, comprising: providing a human animalhaving a lung, said lung having a pulmonary cell on a membrane surfaceof the lung, said cell having a viral receptor; and inhaling a linkermolecule into the lung, said linker molecule having a polymer covalentlyattached thereto, wherein the inhaling results in the linker moleculebeing covalently bonded to the membrane surface such that the polymerprevents an extracellular virus from bonding to the viral receptor. 48.A method for forming a chemo-physiological structure, comprising:providing a human animal having a vagina, said vagina having a vaginalcell on a membrane surface of the vagina said cell having a viralreceptor; and inhaling a linker molecule into the lung, said linkermolecule having a polymer covalently attached thereto, wherein theinhaling results in the linker molecule being covalently bonded to themembrane surface such that the polymer prevents an extracellular virusfrom bonding to the viral receptor.
 49. A chemo-physiological structure,comprising: a membrane surface of a cell of an animal and a viralreceptor coupled to the membrane surface; and means for covalentlybonding a linker molecule to a tissue member selected from the groupconsisting of the membrane surface, the viral receptor, and acombination thereof, wherein a polymer is covalently attached to thelinker molecule, and wherein the polymer prevents an extracellular virusfrom bonding to the viral receptor.
 50. A chemo-physiological structure,comprising: a membrane surface of a cell of an animal and a viralreceptor coupled to the membrane surface; and means for covalentlybonding a linker molecule bonded to the viral receptor, wherein apolymer is covalently attached to the linker molecule, and wherein thepolymer prevents an extracellular virus from bonding to the viralreceptor.
 51. A chemo-physiological structure, comprising: a membranesurface of a cell of an animal and a viral receptor coupled to themembrane surface; and means for covalently bonding a linker molecule toa lysine group at a tissue member selected from the group consisting ofthe membrane surface, the viral receptor, and a combination thereof,wherein a polymer is covalently attached to the linker molecule, andwherein the polymer prevents an extracellular virus from bonding to theviral receptor.
 52. A chemo-physiological structure, comprising: amembrane surface of a cell of an animal and a viral receptor coupled tothe membrane surface, said cell selected from the group consisting of anepithelial cell and an endothelial cell; and means for covalentlybonding a linker molecule to a lysine group at a tissue member selectedfrom the group consisting of the membrane surface, the viral receptor,and a combination thereof, wherein a polymer is covalently attached tothe linker molecule, and wherein the polymer prevents an extracellularvirus from bonding to the viral receptor.
 53. A chemo-physiologicalstructure, comprising: a membrane surface of a nasal epithelial cell ofan animal and a viral receptor coupled to the membrane surface; andmeans for covalently bonding a linker molecule to a tissue memberselected from the group consisting of the membrane surface, the viralreceptor, and a combination thereof, wherein a polymer is covalentlyattached to the linker molecule, and wherein the polymer prevents anextracellular virus from bonding to the viral receptor.
 54. Achemo-physiological structure, comprising: a membrane surface of apulmonary cell of an animal and a viral receptor coupled to the membranesurface; and means for covalently bonding a linker molecule to a tissuemember selected from the group consisting of the membrane surface, theviral receptor, and a combination thereof, wherein a polymer iscovalently attached to the linker molecule, and wherein the polymerprevents an extracellular virus from bonding to the viral receptor. 55.A chemo-physiological structure, comprising: a membrane surface of avaginal cell of an animal and a viral receptor coupled to the membranesurface; and means for covalently bonding a linker molecule to a tissuemember selected from the group consisting of the membrane surface, theviral receptor, and a combination thereof, wherein a polymer iscovalently attached to the linker molecule, and wherein the polymerprevents an extracellular virus from bonding to the viral receptor. 56.A chemo-physiological structure, comprising: an animal having a cellsuch that a viral receptor is coupled to a membrane surface of the cell;and means for covalently bonding a linker molecule to a tissue memberselected from the group consisting of the membrane surface, the viralreceptor, and a combination thereof, wherein a polymer is covalentlyattached to the linker molecule, and wherein the polymer prevents anextracellular virus from bonding to the viral receptor.
 57. Achemo-physiological structure, comprising: a human animal having a cellsuch that a viral receptor is coupled to a membrane surface of the cell;and means for covalently bonding a linker molecule to a tissue memberselected from the group consisting of the membrane surface, the viralreceptor, and a combination thereof, wherein a polymer is covalentlyattached to the linker molecule, and wherein the polymer prevents anextracellular virus from bonding to the viral receptor.
 58. Achemo-physiological structure, comprising: a veterinary animal having acell such that a viral receptor is coupled to a membrane surface of thecell; and means for covalently bonding a linker molecule to a tissuemember selected from the group consisting of the membrane surface, theviral receptor, and a combination thereof, wherein a polymer iscovalently attached to the linker molecule, and wherein the polymerprevents an extracellular virus from bonding to the viral receptor. 59.A chemo-physiological structure, comprising: an animal having a cellsuch that a viral receptor is coupled to a membrane surface of the cell;and means for covalently bonding a linker molecule to a tissue memberselected from the group consisting of the membrane surface, the viralreceptor, and a combination thereof, wherein a polymer is covalentlyattached to the linker molecule, and wherein the polymer has a longchain length that prevents an extracellular virus from bonding to theviral receptor.
 60. A chemo-physiological structure, comprising: ananimal having a cell such that a viral receptor is coupled to a membranesurface of the cell; and means for covalently bonding a linker moleculeto a tissue member selected from the group consisting of the membranesurface, the viral receptor, and a combination thereof, wherein apolymer inactivates a charge-charge interaction that would otherwisebind an extracellular virus to the viral receptor.
 61. Achemo-physiological structure, comprising: an animal having a cell suchthat a viral receptor is coupled to a membrane surface of the cell; andmeans for covalently bonding a linker molecule to a tissue memberselected from the group consisting of the membrane surface, the viralreceptor, and a combination thereof, wherein a polymer is covalentlyattached to the linker molecule, and wherein the polymer prevents anextracellular virus from entering an interior portion of the cell.
 62. Achemo-physiological structure, comprising: an animal having a cell suchthat a viral receptor is coupled to a membrane surface of the cell, saidcell selected from the group consisting of an epithelial cell and anendothelial cell; and means for covalently bonding a linker molecule toa tissue member selected from the group consisting of the membranesurface, the viral receptor, and a combination thereof, wherein apolymer is covalently attached to the linker molecule, and wherein thepolymer prevents an extracellular virus from entering an interiorportion of the cell.
 63. A chemo-physiological structure, comprising: ananimal having a nasal cavity, said nasal cavity having a nasalepithelial cell on an nasal membrane surface, said cell having a viralreceptor; and means for spraying a linker molecule into the nasalcavity, said linker molecule having a polymer covalently attachedthereto, wherein the spraying results in the linker molecule beingcovalently bonded to the membrane surface such that the polymer preventsan extracellular virus from bonding to the viral receptor.
 64. Achemo-physiological structure, comprising: a human animal having a lung,said lung having a pulmonary cell on a membrane surface, said cellhaving a viral receptor; and means for inhaling a linker molecule intothe lung, said linker molecule having a polymer covalently attachedthereto, wherein the inhaling results in the linker molecule beingcovalently bonded to the membrane surface such that the polymer preventsan extracellular virus from bonding to the viral receptor.
 65. Achemo-physiological structure, comprising: a human animal having avagina, said vagina having a vaginal cell on a membrane surface, saidcell having a viral receptor; and means for inhaling a linker moleculeinto the lung, said linker molecule having a polymer covalently attachedthereto, wherein the inhaling results in the linker molecule beingcovalently bonded to the membrane surface such that the polymer preventsan extracellular virus from bonding to the viral receptor.
 66. Achemo-physiological structure, comprising: a virus having a capsid; anda linker molecule covalently bonded to the capsid, wherein a polymer iscovalently attached to the linker molecule, and wherein the polymerenvelops the virus in a manner that prevents the virus from bonding to acell of an animal.
 67. A chemo-physiological structure, comprising: avirus having a capsid, wherein the virus does not include a SimianVacuolating Agent virus; and a linker molecule covalently bonded to thecapsid, wherein a polymer is covalently attached to the linker molecule,and wherein the polymer envelops the virus in a manner that prevents thevirus from bonding to a cell of an animal.
 68. A chemo-physiologicalstructure, comprising: a virus having a capsid; and a linker moleculecovalently bonded to the capsid, wherein a polymer is covalentlyattached to the linker molecule, and wherein the polymer envelops thevirus in a manner that prevents the virus from bonding to a cell of ananimal, and wherein the cell is not a monkey kidney cell.
 69. Achemo-physiological structure, comprising: a virus having a capsid; anda linker molecule covalently bonded to the capsid, wherein the linkermolecule includes cyanuric chloride, wherein a polymer is covalentlyattached to the linker molecule, and wherein the polymer envelops thevirus in a manner that prevents the virus from bonding to a cell of ananimal.
 70. A chemo-physiological structure, comprising: a virus havinga capsid; and a linker molecule covalently bonded to the capsid, whereinthe linker molecule is selected from the group consisting of imidazolylformate, succinimidyl succinate, succinimidyl glutarate,N-hydroxysuccinimide, 4-Nitrophenol, 2,4,5-trichlorophenol, and achloroformate, wherein a polymer is covalently attached to the linkermolecule, and wherein the polymer envelops the virus in a manner thatprevents the virus from bonding to a cell of an animal.
 71. Achemo-physiological structure, comprising: a virus having a capsid; anda linker molecule covalently bonded to the capsid, wherein the linkermolecule does not include cyanuric chloride, wherein a polymer iscovalently attached to the linker molecule, and wherein the polymerenvelops the virus in a manner that prevents the virus from bonding to acell of an animal.
 72. A chemo-physiological structure, comprising: avirus having a capsid; and a linker molecule covalently bonded to thecapsid, wherein a polymer is covalently attached to the linker molecule,wherein the polymer includes methoxypolyethylene glycol, and wherein thepolymer envelops the virus in a manner that prevents the virus frombonding to a cell of an animal.
 73. A chemo-physiological structure,comprising: a virus having a capsid; and a linker molecule covalentlybonded to the capsid, wherein a polymer is covalently attached to thelinker molecule, wherein the polymer wherein the polymer is selectedfrom the group consisting of polyethylene glycol, ethoxypolyethyleneglycol, dextran, ficoll, and arabinogalactan, and wherein the polymerenvelops the virus in a manner that prevents the virus from bonding to acell of an animal.
 74. A chemo-physiological structure, comprising: avirus having a capsid; and a linker molecule covalently bonded to thecapsid, wherein a polymer is covalently attached to the linker molecule,wherein the polymer does not include methoxypolyethylene glycol, andwherein the polymer envelops the virus in a manner that prevents thevirus from bonding to a cell of an animal.
 75. A chemo-physiologicalstructure, comprising: a virus having a capsid, wherein the virus hashuman significance; and a linker molecule covalently bonded to thecapsid, wherein a polymer is covalently attached to the linker molecule,and wherein the polymer envelops the virus in a manner that prevents thevirus from bonding to a cell of an animal.
 76. A chemo-physiologicalstructure, comprising: a virus having a capsid, wherein the virus hasveterinary significance; and a linker molecule covalently bonded to thecapsid, wherein a polymer is covalently attached to the linker molecule,and wherein the polymer envelops the virus in a manner that prevents thevirus from bonding to a cell of an animal.
 77. A chemo-physiologicalstructure, comprising: a virus having a capsid; and a linker moleculecovalently bonded to an amino acid at the capsid, wherein a polymer iscovalently attached to the linker molecule, and wherein the polymerenvelops the virus in a manner that prevents the virus from bonding to acell of an animal.
 78. A chemo-physiological structure, comprising: avirus having a capsid; and a linker molecule covalently bonded to alysine group at the capsid, wherein a polymer is covalently attached tothe linker molecule, and wherein the polymer envelops the virus in amanner that prevents the virus from bonding to a cell of an animal. 79.A chemo-physiological structure, comprising: a virus having a capsid;and a linker molecule covalently bonded to a carbohydrate at the capsid,wherein a polymer is covalently attached to the linker molecule, andwherein the polymer envelops the virus in a manner that prevents thevirus from bonding to a cell of an animal.
 80. A chemo-physiologicalstructure, comprising: a virus having a capsid; and a linker moleculecovalently bonded to a sulfhydryl group at the capsid, wherein a polymeris covalently attached to the linker molecule, and wherein the polymerenvelops the virus in a manner that prevents the virus from bonding to acell of an animal.
 81. A chemo-physiological structure, comprising: avirus having a capsid; a cell of an animal; and a linker moleculecovalently bonded to the capsid, wherein a polymer is covalentlyattached to the linker molecule, and wherein the polymer envelops thevirus in a manner that prevents the virus from bonding to the cell. 82.A chemo-physiological structure, comprising: a virus having a capsid; acell of an animal, wherein the cell is not a monkey kidney cell; and alinker molecule covalently bonded to the capsid, wherein a polymer iscovalently attached to the linker molecule, and wherein the polymerenvelops the virus in a manner that prevents the virus from bonding tothe cell.
 83. A chemo-physiological structure, comprising: a virushaving a capsid; a cell of an animal, wherein the cell is selected fromthe group consisting of an epithelial cell and an endothelial cell; anda linker molecule covalently bonded to the capsid, wherein a polymer iscovalently attached to the linker molecule, and wherein the polymerenvelops the virus in a manner that prevents the virus from bonding tothe cell.
 84. A chemo-physiological structure, comprising: a virushaving a capsid; a cell of an animal, wherein the cell is a nasalepithelial cell; and a linker molecule covalently bonded to the capsid,wherein a polymer is covalently attached to the linker molecule, andwherein the polymer envelops the virus in a manner that prevents thevirus from bonding to the cell.
 85. A chemo-physiological structure,comprising: a virus having a capsid; a cell of an animal, wherein thecell is a pulmonary cell; and a linker molecule covalently bonded to thecapsid, wherein a polymer is covalently attached to the linker molecule,and wherein the polymer envelops the virus in a manner that prevents thevirus from bonding to the cell.
 86. A chemo-physiological structure,comprising: a virus having a capsid; a cell of an animal, wherein thecell is a vaginal cell; and a linker molecule covalently bonded to thecapsid, wherein a polymer is covalently attached to the linker molecule,and wherein the polymer envelops the virus in a manner that prevents thevirus from bonding to the cell.
 87. A chemo-physiological structure,comprising: a virus having a capsid; an animal; and a linker moleculecovalently bonded to the capsid, wherein a polymer is covalentlyattached to the linker molecule, and wherein the polymer envelops thevirus in a manner that prevents the virus from bonding to a cell of theanimal.
 88. A chemo-physiological structure, comprising: a virus havinga capsid; a human animal; and a linker molecule covalently bonded to thecapsid, wherein a polymer is covalently attached to the linker molecule,and wherein the polymer envelops the virus in a manner that prevents thevirus from bonding to a cell of the animal.
 89. A chemo-physiologicalstructure, comprising: a virus having a capsid; a veterinary animal; anda linker molecule covalently bonded to the capsid, wherein a polymer iscovalently attached to the linker molecule, and wherein the polymerenvelops the virus in a manner that prevents the virus from bonding to acell of the animal.
 90. A chemo-physiological structure, comprising: avirus having a capsid; and a linker molecule covalently bonded to thecapsid, wherein a polymer is covalently attached to the linker molecule,and wherein the polymer has a long chain length that causes the polymerto envelop the virus in a manner that prevents the virus from bonding toa cell of an animal.
 91. A chemo-physiological structure, comprising: avirus having a capsid; and a linker molecule covalently bonded to thecapsid, wherein a polymer is covalently attached to the linker molecule,and wherein the polymer inactivates a charge-charge interaction thatwould otherwise bind the virus to a cell of an animal.
 92. Achemo-physiological structure, comprising: a virus having a capsid; anda linker molecule covalently bonded to the capsid, wherein a polymer iscovalently attached to the linker molecule, and wherein the polymerenvelops the virus in a manner that prevents the virus from entering aninterior portion of a cell of an animal.
 93. A method for forming achemo-physiological structure, comprising: providing a virus having acapsid; and covalently bonding a linker molecule to the capsid, whereina polymer is covalently attached to the linker molecule, and wherein thepolymer envelops the virus in a manner that prevents the virus frombonding to a cell of an animal.
 94. A method for forming achemo-physiological structure, comprising: providing a virus having acapsid, wherein the virus does not include a Simian Vacuolating Agentvirus; and covalently bonding a linker molecule to the capsid, wherein apolymer is covalently attached to the linker molecule, and wherein thepolymer envelops the virus in a manner that prevents the virus frombonding to a cell of an animal.
 95. A method for forming achemo-physiological structure, comprising: providing a virus having acapsid; and covalently bonding a linker molecule to the capsid, whereina polymer is covalently attached to the linker molecule, wherein thepolymer envelops the virus in a manner that prevents the virus frombonding to a cell of an anima animal, and wherein the cell is not amonkey kidney cell.
 96. A method for forming a chemo-physiologicalstructure, comprising: providing a virus having a capsid; and covalentlybonding a linker molecule to the capsid, wherein the linker moleculeincludes cyanuric chloride, wherein a polymer is covalently attached tothe linker molecule, and wherein the polymer envelops the virus in amanner that prevents the virus from bonding to a cell of an animal. 97.A method for forming a chemo-physiological structure, comprising:providing a virus having a capsid; and covalently bonding a linkermolecule to the capsid, wherein the linker molecule is selected from thegroup consisting of imidazolyl formate, succinimidyl succinate,succinimidyl glutarate, N-hydroxysuccinimide, 4-Nitrophenol,2,4,5-trichlorophenol, and a chloroformate, wherein a polymer iscovalently attached to the linker molecule, and wherein the polymerenvelops the virus in a manner that prevents the virus from bonding to acell of an animal.
 98. A method for forming a chemo-physiologicalstructure, comprising: providing a virus having a capsid; and covalentlybonding a linker molecule to the capsid, wherein the linker moleculedoes not include cyanuric chloride, wherein a polymer is covalentlyattached to the linker molecule, and wherein the polymer envelops thevirus in a manner that prevents the virus from bonding to a cell of ananimal.
 99. A method for forming a chemo-physiological structure,comprising: providing a virus having a capsid; and covalently bonding alinker molecule to the capsid, wherein a polymer is covalently attachedto the linker molecule, wherein the polymer includes methoxypolyethyleneglycol, and wherein the polymer envelops the virus in a manner thatprevents the virus from bonding to a cell of an animal.
 100. A methodfor forming a chemo-physiological structure, comprising: providing avirus having a capsid; and covalently bonding a linker molecule to thecapsid, wherein a polymer is covalently attached to the linker molecule,wherein the polymer wherein the polymer is selected from the groupconsisting of polyethylene glycol, ethoxypolyethylene glycol, dextran,ficoll, and arabinogalactan, and wherein the polymer envelops the virusin a manner that prevents the virus from bonding to a cell of an animal.101. A method for forming a chemo-physiological structure, comprising:providing a virus having a capsid; and covalently bonding a linkermolecule to the capsid, wherein a polymer is covalently attached to thelinker molecule, wherein the polymer does not includemethoxypolyethylene glycol, and wherein the polymer envelops the virusin a manner that prevents the virus from bonding to a cell of an animal.102. A method for forming a chemo-physiological structure, comprising:providing a virus having a capsid, wherein the virus has humansignificance; and covalently bonding a linker molecule to the capsid,wherein a polymer is covalently attached to the linker molecule, andwherein the polymer envelops the virus in a manner that prevents thevirus from bonding to a cell of an animal.
 103. A method for forming achemo-physiological structure, comprising: providing a virus having acapsid, wherein the virus has veterinary significance; and covalentlybonding a linker molecule to the capsid, wherein a polymer is covalentlyattached to the linker molecule, and wherein the polymer envelops thevirus in a manner that prevents the virus from bonding to a cell of ananimal.
 104. A method for forming a chemo-physiological structure,comprising: providing a virus having a capsid; and covalently bonding alinker molecule to an amino acid at the capsid, wherein a polymer iscovalently attached to the linker molecule, and wherein the polymerenvelops the virus in a manner that prevents the virus from bonding to acell of an animal.
 105. A method for forming a chemo-physiologicalstructure, comprising: providing a virus having a capsid; and covalentlybonding a linker molecule to a lysine group at the capsid, wherein apolymer is covalently attached to the linker molecule, and wherein thepolymer envelops the virus in a manner that prevents the virus frombonding to a cell of an animal.
 106. A method for forming achemo-physiological structure, comprising: providing a virus having acapsid; and covalently bonding a linker molecule to a carbohydrate atthe capsid, wherein a polymer is covalently attached to the linkermolecule, and wherein the polymer envelops the virus in a manner thatprevents the virus from bonding to a cell of an animal.
 107. A methodfor forming a chemo-physiological structure, comprising: providing avirus having a capsid; and covalently bonding a linker molecule to asulfhydryl group at the capsid, wherein a polymer is covalently attachedto the linker molecule, and wherein the polymer envelops the virus in amanner that prevents the virus from bonding to a cell of an animal. 108.A method for forming a chemo-physiological structure, comprising:providing a virus having a capsid; providing a cell of an animal; andcovalently bonding a linker molecule to the capsid, wherein a polymer iscovalently attached to the linker molecule, and wherein the polymerenvelops the virus in a manner that prevents the virus from bonding tothe cell.
 109. A method for forming a chemo-physiological structure,comprising: providing a virus having a capsid; providing a cell of ananimal, wherein the cell is not a monkey kidney cell; and covalentlybonding a linker molecule to the capsid, wherein a polymer is covalentlyattached to the linker molecule, and wherein the polymer envelops thevirus in a manner that prevents the virus from bonding to the cell. 110.A method for forming a chemo-physiological structure, comprising:providing a virus having a capsid; providing a cell of an animal,wherein the cell is selected from the group consisting of an epithelialcell and an endothelial cell; and covalently bonding a linker moleculeto the capsid, wherein a polymer is covalently attached to the linkermolecule, and wherein the polymer envelops the virus in a manner thatprevents the virus from bonding to the cell.
 111. A method for forming achemo-physiological structure, comprising: providing a virus having acapsid; providing a cell of an animal, wherein the cell is a nasalepithelial cell; and covalently bonding a linker molecule to the capsid,wherein a polymer is covalently attached to the linker molecule, andwherein the polymer envelops the virus in a manner that prevents thevirus from bonding to the cell.
 112. A method for forming achemo-physiological structure, comprising: providing a virus having acapsid; providing a cell of an animal, wherein the cell is a pulmonarycell; and covalently bonding a linker molecule to the capsid, wherein apolymer is covalently attached to the linker molecule, and wherein thepolymer envelops the virus in a manner that prevents the virus frombonding to the cell.
 113. A method for forming a chemo-physiologicalstructure, comprising: providing a virus having a capsid; providing acell of an animal, wherein the cell is a vaginal cell; and covalentlybonding a linker molecule to the capsid, wherein a polymer is covalentlyattached to the linker molecule, and wherein the polymer envelops thevirus in a manner that prevents the virus from bonding to the cell. 114.A method for forming a chemo-physiological structure, comprising:providing a virus having a capsid; providing an animal; and covalentlybonding a linker molecule to the capsid, wherein a polymer is covalentlyattached to the linker molecule, and wherein the polymer envelops thevirus in a manner that prevents the virus from bonding to the cell. 115.A method for forming a chemo-physiological structure, comprising:providing a virus having a capsid; providing a human animal; andcovalently bonding a linker molecule to the capsid, wherein a polymer iscovalently attached to the linker molecule, and wherein the polymerenvelops the virus in a manner that prevents the virus from bonding tothe cell.
 116. A method for forming a chemo-physiological structure,comprising: providing a virus having a capsid; providing a veterinaryanimal; and covalently bonding a linker molecule to the capsid, whereina polymer is covalently attached to the linker molecule, and wherein thepolymer envelops the virus in a manner that prevents the virus frombonding to the cell.
 117. A chemo-physiological structure, comprising: amembrane surface of a cell of an animal; a viral receptor coupled to themembrane surface; a first linker molecule covalently bonded to a tissuemember selected from the group consisting of the membrane surface, theviral receptor, and a combination thereof, wherein a first polymer iscovalently attached to the linker molecule, and wherein the firstpolymer prevents an extracellular virus from bonding to the viralreceptor; the extracellular virus having a capsid; and a second linkermolecule covalently bonded to the capsid, wherein a second polymer iscovalently attached to the second linker molecule, and wherein thesecond polymer envelops the extracellular virus in a manner thatprevents the extracellular virus from bonding to the cell of the animal.118. The chemo-physiological structure of claim 117, wherein the firstlinker molecule and the second linker molecule are chemically identical,and wherein the first polymer and the second polymer are chemicallyidentical.
 119. A chemo-physiological structure, comprising: an animal;a membrane surface of a cell within the animal; a viral receptor coupledto the membrane surface; a first linker molecule covalently bonded to atissue member selected from the group consisting of the membranesurface, the viral receptor, and a combination thereof, wherein a firstpolymer is covalently attached to the linker molecule, and wherein thefirst polymer prevents an extracellular virus from bonding to the viralreceptor; the extracellular virus having a capsid; and a second linkermolecule covalently bonded to the capsid, wherein a second polymer iscovalently attached to the second linker molecule, wherein the secondpolymer envelops the extracellular virus in a manner that prevents theextracellular virus from bonding to the cell of the animal, wherein thefirst linker molecule and the second linker molecule are chemicallyidentical, and wherein the first polymer and the second polymer arechemically identical.
 120. A method for forming a chemo-physiologicalstructure, comprising: providing a membrane surface of a cell of ananimal and a viral receptor coupled to the membrane surface; covalentlybonding a first linker molecule to a tissue member selected from thegroup consisting of the membrane surface, the viral receptor, and acombination thereof, wherein a first polymer is covalently attached tothe linker molecule, and wherein the first polymer prevents anextracellular virus from bonding to the viral receptor; providing theextracellular virus having a capsid; and covalently bonding a secondlinker molecule to the capsid, wherein a second polymer is covalentlyattached to the second linker molecule, and wherein the second polymerenvelops the extracellular virus in a manner that prevents theextracellular virus from bonding to the cell of the animal.
 121. Themethod of claim 120, wherein the first linker molecule and the secondlinker molecule are chemically identical, and wherein the first polymerand the second polymer are chemically identical.
 122. A method forforming a chemo-physiological structure, comprising: providing an animalhaving a cell such that a viral receptor is coupled to a membranesurface of the cell; covalently bonding a first linker molecule to atissue member selected from the group consisting of the membranesurface, the viral receptor, and a combination thereof, wherein a firstpolymer is covalently attached to the linker molecule, and wherein thefirst polymer prevents an extracellular virus from bonding to the viralreceptor; providing the extracellular virus having a capsid; andcovalently bonding a second linker molecule to the capsid, wherein asecond polymer is covalently attached to the second linker molecule,wherein the second polymer envelops the extracellular virus in a mannerthat prevents the extracellular virus from bonding to the cell of theanimal, wherein the first linker molecule and the second linker moleculeare chemically identical, and wherein the first polymer and the secondpolymer are chemically identical.
 123. A chemo-physiological structure,comprising: providing a membrane surface of a cell of an animal and aviral receptor coupled to the membrane surface; means for covalentlybonding a first linker molecule to a tissue member selected from thegroup consisting of the membrane surface, the viral receptor, and acombination thereof, wherein a first polymer is covalently attached tothe linker molecule, and wherein the first polymer prevents anextracellular virus from bonding to the viral receptor; providing theextracellular virus having a capsid; and means for covalently bonding asecond linker molecule to the capsid, wherein a second polymer iscovalently attached to the second linker molecule, and wherein thesecond polymer envelops the extracellular virus in a manner thatprevents the extracellular virus from bonding to the cell of the animal.124. The chemo-physiological structure of claim 123, wherein the firstlinker molecule and the second linker molecule are chemically identical,and wherein the first polymer and the second polymer are chemicallyidentical.
 125. A chemo-physiological structure, comprising: an animalhaving a cell such that a viral receptor is coupled to a membranesurface of the cell; means for covalently bonding a first linkermolecule to a tissue member selected from the group consisting of themembrane surface, the viral receptor, and a combination thereof, whereina first polymer is covalently attached to the linker molecule, andwherein the first polymer prevents an extracellular virus from bondingto the viral receptor; the extracellular virus having a capsid; andmeans for covalently bonding a second linker molecule to the capsid,wherein a second polymer is covalently attached to the second linkermolecule, wherein the second polymer envelops the extracellular virus ina manner that prevents the extracellular virus from bonding to the cellof the animal, wherein the first linker molecule and the second linkermolecule are chemically identical, and wherein the first polymer and thesecond polymer are chemically identical.